Another one of the top genes in our study, ARHGEF10, is similarly involved in several cellular and actin cytoskeleton processes. As a member of the large family of rho guanine-nucleotide-exchange factors (GEFs), ARHGEF10 acts as a molecular switch in the regulation of signal transduction pathways [50], binding to G-protein coupled receptors to stimulate downstream binding with protein kinases to affect cell signaling and extracellular stimuli processed through Rho proteins to modulate the intracellular actin cytoskeleton and subsequently intracellular processing [51,52]. Genetic studies in dogs suggest its role in neuropathies; a mutation in the gene resulted in a severe form of juvenile-onset polyneuropathy, which bears clinical similarity to the group of neuropathies termed Charcot-Marie-Tooth disease in humans [53]. Though expressed in multiple tissues, it has higher expression in the spinal cord and dorsal root ganglion [54]. Another gene showing nominal association (p≤0.001), RASGRP2 (RAS guanyl releasing protein 2), encodes a brain-enriched nucleotide that contains an N-terminal GEF domain and may also play a role in cell signaling. The emerging functional themes related to the top genes in our data appear to
